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Lung CancerPhase 2NCT03292133

A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer

A Phase 2 study testing EGF816 and Gefitinib in people with Lung Cancer, run by Massachusetts General Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This research study is studying a combination of drugs as a possible treatment for EGFR mutation-positive lung cancer. The drugs involved in this study are: EGF816 Gefitinib Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
EGF816 and Gefitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
31 Oct 2017to 4 Mar 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have a pathologically-confirmed diagnosis of non-small cell lung cancer (NSCLC).
  • Participants must have advanced disease - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/IASLC 7th edition proposed staging criteria
  • An EGFR sensitizing mutation must be detected in tumor tissue. Specifically, patients harboring the most common mutations, deletions in exon 19 or the L858R mutation in exon 21 are eligible. Other EGFR sensitizing mutations may be eligible after discussion with the principal investigator. Patients may be enrolled in the study based on an activating EGFR mutation detected by a CLIA-certified tissue or plasma-based assay, but will be required to undergo a mandatory tumor biopsy during study screening.
  • Participants must have measurable disease, per RECIST 1.1. See Section 11 for the evaluation of measurable disease.
  • Patients in the six patient safety run-in cohort may have had a prior EGFR TKI in the metastatic setting (to allow for patients who started initial therapy at an outside hospital), but treatment duration must have been less than three months. After the initial six-patient safety run-in, no prior EGFR TKI therapy in the metastatic setting is allowed. An EGFR TKI given in the adjuvant setting (i.e. with no measurable disease at the time of administration) is allowable provided the subject has been off of EGFR TKI therapy for at least six months at the time of enrollment.
  • Patients may have had no more than one prior line of chemotherapy or immunotherapy in the metastatic setting. At least 14 days must have elapsed from the last chemo/immunotherapy administration until the start of protocol treatment, and patients must have recovered from the side effects of any of these agents.
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  • Patients must be screened for HBV. Patients who are either HBsAg positive or HBV-DNA positive must be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of study treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816. Additional management of the patients would be provided by a physician with expertise in management of HBV, if needed. Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
  • Patients must receive insurance approval for or be willing to pay for commercial gefitinib.
  • Age >/= 18 years.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • Life expectancy of greater than 12 weeks.
  • Participants must have normal organ and marrow function as defined below:
  • Leukocytes ≥3,000/mcL
  • Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Total bilirubin >1.5 x upper limit of normal (ULN)
  • For patients with Gilbert's syndrome total bilirubin >3.0 x ULN
  • AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal; for patients with known hepatic metastases AST and/or ALT > 5x ULN
  • Creatinine ≤1.5 × institutional upper limit of normal
  • The effects of EGF816 and gefitinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use highly effective contraception during the study and for 3 months after stopping the study treatment. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptom thermal, postovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male Partner: male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
  • Combination of any two of the following (a+b or a+c, or b+c):
  • A. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
  • B. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • C. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
  • D. In case of use of oral contraception women should have been stable on the same pill for a minimum of 30 days before taking study treatment.
  • Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.
  • Sexually active males must agree to use a condom during intercourse while taking drug and for 3 months after stopping treatment; men should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
  • Ability to understand and the willingness to sign a written informed consent document. Written informed consent must be obtained prior to any screening procedures.

Who cannot join

  • Participants with clinically active or symptomatic interstitial lung disease or interstitial pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention) and patients with history of clinically significant interstitial lung disease or radiation pneumonitis.
  • Patients with clinically symptomatic brain metastases or leptomeningeal disease. Patients may be on a stable dose of corticosteroids to control brain metastases if they have been on a stable dose for two weeks prior to study treatment and are clinically asymptomatic.
  • Patients who have had radiation to the lung fields within four weeks of starting treatment. For patients receiving palliative radiation to thoracic vertebrae, ribs or other sites where the radiation field includes the lungs, radiation must be completed at least two weeks before starting treatment. For all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting to treatment. At least six months must have elapsed from radiation given with curative intent.
  • Patients who have had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 2 weeks prior to starting study drug or who have not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the study ≥1 week after the procedure.
  • Patients unable or unwilling to undergo a biopsy for research during the screening period, 2-3 weeks into the course of therapy and at the time of progression.
  • Patients with a second, clinically active, cancer. Patients with second cancers which have been treated with curative intent and/or are currently inactive are allowed.
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  • Patients who have undergone a bone marrow or solid organ transplant.
  • Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory).
  • Participants who are receiving any other investigational agents. Patients previously treated with investigational agents must complete a washout period of at least one week or five half-lives, whichever is longer, before starting treatment.
  • Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use, except those on steroid to control brain metastases, those on topical or inhaled steroids, or steroids given via local injection.
  • Patients with clinically significant, uncontrolled cardiovascular disease, such as:
  • Unstable angina within 6 months prior to screening
  • Myocardial infarction within 6 months prior to screening
  • Patients with a history of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Peripheral vascular disease
  • Patients with uncontrolled hypertension defined as a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening
  • Ventricular arrhythmias
  • Supraventricular and nodal arrhythmias not controlled with medication
  • Other cardiac arrhythmia not controlled with medication
  • Patients with corrected QT (QTc) ≥450 ms (male patients) or ≥460 ms (female patients) using Fridericia correction (QTcF) on the screening ECG (using triplicate ECGs)
  • Patients with history of congenital long QT syndrome or history of torsade de pointes
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to EGF816 or gefitinib.
  • Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
  • Unable or unwilling to swallow tablets or capsules.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because the effects of EGF816 and gefitinib on a developing fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with EGF816 or gefitinib, breastfeeding should be discontinued if the mother is treated with EGF816 and gefitinib

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

Other trials in United States

About this study

Official title: A Phase 2 Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer

This research study is studying a combination of drugs as a possible treatment for EGFR mutation-positive lung cancer.

The drugs involved in this study are:

  • EGF816
  • Gefitinib
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease or patient population. "Investigational" means that the drug or drugs are being studied and have not been approved together for patients.

The FDA (the U.S. Food and Drug Administration) has approved gefitinib as a treatment option for EGFR mutation-positive lung cancer.

The FDA has not approved EGF816 as a treatment for any disease at this time.

In this research study, the investigators are studying the safety and efficacy of the combination of the study drugs EGF816 and gefitinib.

Both EGF816 and gefitinib are inhibitors which target a specific mutation in cancer and may stop tumors growing and multiplying.

Conditions
Lung Cancer
Being tested
EGF816, Gefitinib
Keywords
Lung Cancer
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EGF816Drug

    EGF816 is an inhibitor which target a specific mutation in cancer and may stop tumors growing and multiplying

  • GefitinibDrug

    Also called Iressa

    Gefitinib is an inhibitor which target a specific mutation in cancer and may stop tumors growing and multiplying

Study groups in NCT03292133
Study groupRoleWhat they receive
EGF816 + GefitinibExperimental* All patients will receive gefitinib orally once daily * EGF816 will be administered orally once daily * Participant will be requested to maintain a medication diary of each dose of medication
Receives: Drug: EGF816; Drug: Gefitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 9 Months Progression Free Rate

    The percentage of participants that are free from objective disease progression or death at 9 months after the start treatment. Progression is evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

    Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: 9 months

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    The number of participants that achieve either a complete response (CR) or a partial response (PR). Response is evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    All CRs and PRs must be confirmed by a second assessment not earlier than 4 weeks after the criteria for response are first met.

    Measured: 4 years and 4 months

  2. Median Overall Survival

    Overall survival is defined as time from the start of treatment until death or loss to follow up. Overall survival will be analyzed using the Kaplan-Meier method.

    Measured: 6 years

  3. Median Progression Free Survival (PFS)

    PFS is defined as the time from start of treatment to the time of objective disease progression, death, or loss to follow up. Progression is evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

    Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Measured: 4.2 years

  4. Summary of Treatment-related Adverse Events

    Treatment-related adverse events, defined as those at least possibly related to study treatment, are summarized below as a measure of patient safety and treatment tolerability. Subjects were evaluated for adverse events by the Common Terminology Criteria for Adverse Events (CTCAE) v4. For each treatment-related event, subjects are counted below by the highest grade they experienced on study per CTCAE v 4.0 to demonstrate the range and severity of treatment-related toxicities documented on study. Grade refers to the severity of the toxicity, with Grade 1 corresponding to mild toxicity, Grade 2 to moderate toxicity, and Grade 3 to severe toxicity. Patients who did not experience a given event at any grade are counted in the final category for each row.

    Measured: Start of treatment through 30 days after the end of treatment (max 4 years and 5 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2017
  2. Study start31 Oct 2017
  3. Primary completion31 Dec 2021
  4. Study completion4 Mar 2025

Why it stopped: Slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03292133
Sponsor's protocol ID
17-291
Status last verified
May 2025
First submitted
21 Sep 2017
Last updated
10 Jun 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing EGF816 and Gefitinib in people with Lung Cancer, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

9 Months Progression Free Rate (time frame: 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03292133.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2025.

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